IRON DEFICIENCY
ANEMIA CHRONIC DISEASE
SIDEROBLASTIC ANEMIA
THALASSEMIA
FOLATE DEFICIENCY
VIT B12 DEFICIENCY
HEREDITARY HEREDITARY SPHEROCYTOSIS
SICKLE CELL ANEMIA
ANEMIAS MICROCYTIC Decreased production of Hb cell divides “extra” time to keep Hb concentration up Decreased levels Hb Microcytic, hypochromic, RDW, Infants- breast feeding, Children- diet total iron heme Hb ferritin, TIBC, serum iron, Adults- peptic ulcer ulcer (males), % sat microcytic anemia menorrhagia (females), Elderly- colon -bicycle tires! polyps/carcinoma; esophageal web -atrophic fissured tongue, spooning Assoc. w/ chronic chronic inflamm or cancer; cancer; in ferritin, TIBC, serum iron, Results in production acute phase % sat hosp. pts reactants from liver, incl. hepcidin (sequesters iron in storage sites to available iron heme Hb microcytic anemia prevent bacteria from getting it) Defective protoporphyrin synthesis -Congenital defects (ALAs) ferritin, TIBC, serum iron, protoporphyrin heme Hb sat (from iron-overloaded state; iron -Acquired causes (alcoholism, lead microcytic anemia laden mitochondria form ring around poisoning b/c inhibits ALAD and nucleus of erythroid precursors (ringer ferrochelatase) sideroblasts) -Lead poisoning: basophilic stippling Decreased synthesis of globin chains Microcytic, hypochromic RBCs with α thal = gene deletion of Hg target cells (incr membrane or decr β thal = gene mutations (point globin Hb microcytic anemia cytoplasm); mutations in promoter or splicing site) Massive erythroid hyperplasia (crew cut X-ray, chipmunk facies) MACROCYTIC Upset in production of DNA precursors cell can’t divide right amount of times Deficiency in folate from diet, Macrocytic RBCs and hypersegmented Develops within months because increased demand, or antagonists neutorphils ( > 5 lobes); stores limited (methotrexate – (methotrexate – inhibits inhibits dihydrofolate homocysteine and normal -treat with folate reductase) methylmalonic acid; glossitis Deficiency B12 due to pernicious anemia (autoimm destruction of parietal cells IF deficiency), pancreatic insuff, rarely diet
Macrocytic RBCs with hypersegmented neutrophils; homocysteine and m ethymalonic ethymalonic acid; glossitis; subacute combined degeneration of spinal cored NORMOCYTIC WITH EXTRAVASCULAR HEMOLYSIS Increased peripheral destruction Inherited defect of RBC cytoskeletonSpherocytes with loss of central palor; membrane tethering proteins (spectrin, RDW, MCHC; splenomegaly, ankrin, band 3.1) abnormal jaundice with unconjugated bilirubin bilirubin & blebbing; gets caught in spleen and increase risk bilirubin gallstones; then eaten by macrophages anemia Howell-Jolly bodies (small dark nuclear remnants) in asplenic patients Auto recessive mutation in β chain of Sickle cells Hb; single amino acid change replaces Target cells normal glutamic acid (hydrophilic) with Howell-Jolly bodies (due to
-Less common and takes years to develop (large hepatic stores) -Shilling test to test for IF -Neuro symptoms not helped with folate…therefore folate…therefore need to give B12
-Diagnosis by osmotic fragility test (spherocytes don’t have enough room to expand for increase in water) -Stable course punctuated by aplastic crisis (parvovirus B19) Screen with metabisulfite and electrophoresis; electrophoresis; increased risk for incfection w/ encapsulated organisms
HEMOGLOBIN C
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
GLUCOSE-6_PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY
IMMUNE HEMOLYTIC ANEMIA (IHA)
Auto recessive mutation of β chain of Hb, glutamic acid replaced by lysine
-HbC crystals seen in RBCs -Target cells
NORMOCYTIC WITH INTRAVASCULAR HEMOLYSIS Increased destruction Acquired defect in myeloid stem cells RBCs, WBCs and platelets lysed; resulting in absent GPI; cells hemoglobinemia, hemoglobinuria (esp. susceptible to destruction by in morning), hemosiderinuria (days complement (absence GPI = absence after hemolysis) DAF) X-linked recessive disorders Heinz bodies (precipitates of denatured reduced half-life of G6PD so cells Hb - need special stain) & bite cells susceptible to oxidative stress (splenic phagocytes pluck out Heinz G6PD NADPH bodies); hemoglobinuria and back pain glutathione oxidative injury by H2O2 intravasc. hemolysis
Mild anemia
Sucrose test – activates complement -main cause death – thrombosis of hepatic, portal or cerebral veins; complications include iron def anemia and AML Two variants -African: mildly reduced half-life mild hemolysis w/ oxidative stress -Mediterranean: markedly reduced half-life marked intravascular hemolysis w/ ox stress Ox stress caused by fava beans or drugs (primaquine) Coombs Test (DAT) -Direct: confirms presence Ab-coated RBCs -Indirect: presence of Abs in patients serum -Occurs with microthrombi (TTP-HUS, DIC, HELLP), prosthetic heart valves, and aortic stenosis -Iron deficiency anemia can occur P falciparium- daily fever P vivax and ovale- fever every other day
1. Warm: IgG-mediated, extravascular Polychromasia; spheroctyes; small hemolysis, spherocytes, SLE fragmented red cell (triangle); 2. Cold: IgM-mediated, intravascular polychromatophilic red cells (big, hemolysis, Reynaud’s, cold agglutinin, bluish); few red cells on smear pneumaniae MICROANGIOPATHIC HEMOLYTIC Mechanical trauma intravascular Schistocytes (helmet cells) ANEMIA hemolysis results from vascular pathology; RBCs destroyed as they pass thru circulation – “cheese cutter” MALARIA Infection of RBCs and liver with Splenomegaly, banana shape Plasmodium transmitted by female Anopheles mosquito; RBCs rupture as part of the Plasmodium life cycle intravasc hemolysis and cyclical fever ANEMIA DUE TO UNDERPRODUCTION Decreased production of RBCs by bone marrow w/ low corrected reticulocyte count PARVOVIRUS B19 Infects progenitor red cells and Treatment supportive; is self-limiting temporarily halts erythropoiesis significant anemia in setting of preexisting marrow stress APLASTIC ANEMIA Damage to hematopoietic stem cells Empty fatty marrow (biopsy)…causes= Treatment includes cessation pancytopenia w/ low reticulocyte count Fanconi anemia – defect in DNA repair causative drugs, supportive care w/ -from drugs, chemicals, viral infection, Diamond-Blackfan anemia – congenital transfusions and marrow-stimulating and autoimmune damage erythroid aplasia factors; immunosuppression can be Telomerase defect helpful MYELOPHTHISIC PROCESS Pathologic process (eg metastatic Teardrop shaped RBCs Hematopoeisis is impared